Production of L-leucine, L-valine and other amino acids via fermentation has been the subject of considerable research. Numerous genera of microorganisms have been employed along with various amino acid analogues. U.S. Pat. No. 3,865,690 teaches production of L-leucine by culturing a strain of Brevibacterium or Corynebacterium made resistant to a leucine antagonist. U.S. Pat. No. 3,970,519 cultures strains of the same genera in the presence of various amino acids to produce L-leucine. From U.S. Pat. No. 3,893,888 it is known that L-valine can be produced from mutant strains of Brevibacterium resistant to .alpha.-amino-.beta.-hydroxy valeric acid (AHV). U.S. Pat. No. 3,688,073 teaches preparation of L-leucine using a microorganism of the genus Corynebacterium in the presence of a "promoter" for isoleucine, methionine, phenylalanine or valine, e.g. azaleucine or AHV. Azaleucine has been used as an analogue for producing L-leucine. See Wang et al, "Fermentation and Enzyme Technology," John Wiley and Sons, Inc., 1979, pages 18-20. U.S. Pat. No. 3,759,789 utilizes cultures of Arthrobacter alkanicus which are resistant to L-threonine. Precursors of L-leucine and L-isoleucine can be added to increase yields.
The following literature is relevant:
1. Araki, Kazumi, H. Ueda and S. Saigusa. Fermentative Production of L-Leucine with Auxotrophic Mutants of Corynebacterium glutamicum. Agr. Biol. Chem. 38(3), 565-572 (1974). PA0 2. Calvo, R. A., and J. M. Calvo. Lack of End-Product Inhibition and Repression on Leucine Synthesis in a Strain of Salmonella typhimurium. Science, 156, 1107-1109 (1967). PA0 3. Kisumi, M., S. Komatsubara and I. Chibata. Leucine Accumulations by Isoleucine Revertants of Serratia marcescens Resistant to .alpha.-Aminobutyric Acid: Lack of Both Feedback Inhibition and Repression, J. Biochem., 73, 107-115 (1973). PA0 4. Tsuchida, T., F. Yoshinaga K. Kubota, H. Momose and S. Okumura. Cultural Conditions for L-Leucine Production by Strain No. 218, a Mutant of Brevibacterium lactofermentum 2256. Agr. Biol. Chem. 39(5), 1149-1153 (1975). PA0 5. Tsuchida, T., and H. Momose. Genetic Changes of Regulatory Mechanisms Occurred in Leucine and Valine Producing Mutants Derived from Brevibacterium lactofermentum 2256. Agr. Biol. Chem. 39(11), 2193-2198 (1975). PA0 6. Tsuchida, T., F. Yoshinaga, K. Kubota, H. Momose and S. Okumura. Production of L-Leucine by a Mutant of Brevibacterium lactofermentum 2256. Agr. Biol. Chem. 38(10), 19097-1911 (1974). PA0 7. Freundlich, M. and J. M. Trela. (1969). Control of isoleucine, valine, and leucine biosynthesis. J. of Bacteriology, 101-106. PA0 8. Izumi, Y., Y. Asano, Y. Tani and K., Ogata. (1977). Formation of valine and leucine by analog-resistant mutants of an obligate methylotroph, Methylomonas aminofaciens. J. Ferment. Technol., 55, 452-458. PA0 9. Kisumi, M., S. Komatsubara and I. Chibata. (1977) Pathway for isoleucine formation from pyruvate by leucine biosynthetic enzymes in leucine-accumulating isoleucine revertants of Serratia marcescens. J. Biochem., 82, 95-103. PA0 10. Kisumi, M., J. Kato, S. Komatsubara, I. Chibata. (1973). Production of isoleucine, valine and leucine by regulatory mutants of Serratia marcescens. "Genetics of Industrial Microorganisms-Bacteria". PA0 11. Rogerson, A., and M. Freundlich. (1969). Control of isoleucine, valine and leucine biosynthesis. VIII. Mechanism of growth inhibition by leucine in relaxed and stringent strains of Escherichia coli K-12. Biochimica et Biophysica Acta, BRA 26302. PA0 12. Szentirmai, A. and I Horvath. (1976). Regulation of branched-chain amino acid biosynthesis. Acta Microbiol. Acad. Sci. Hung., 23, 137-149. PA0 13. Umbarger, H. E. (1974). The elements involved in the multivalent regulation of the isoleucine and valine biosynthetic enzymes of the Enterobacteriaceae. Proceedings of the 1st. Intersectional Congress of IAMS, 1, Tokyo. PA0 14. Umbarger, H. E. (1973). Genetic and physiological regulation of the isoleucine, valine and leucine biosynthetic enzymes of the Enterobacteriaceae. From "Genetics of Industrial Microorganisms." PA0 15. Umbarger, H. E. (1978). Amino Acid Biosynthesis and Its Regulation. Ann. Rev. Biochem., 47, 533-606, 563.
Several general articles on biosynthetic pathways for producing L-leucine as well as other amino acids have also been published. See: